title: Tubular atrophy and low netrin-1 gene expression are associated with delayed kidney allograft function.
abstract: BACKGROUND
  Delayed graft function (DGF) caused by ischemia/reperfusion injury (I/RI) negatively influences the outcome of kidney transplantation. This prospective single-center study characterized the intrarenal transcriptome during I/RI as a means of identifying genes associated with DGF development.
  
  
  METHODS
  Characterization of the intrarenal transcription profile associated with I/RI was carried out on three sequential graft biopsies from respective allografts before and during transplantation. The intragraft expression of 92 candidate genes was measured using quantitative real-time reverse transcriptase polymerase chain reaction (2) in delayed (n=9) and primary function allografts (n=26).
  
  
  RESULTS
  Cold storage was not associated with significant changes to the expression profile of the target gene transcripts; however, up-regulation of 16 genes associated with enhanced activation of innate and adaptive immune responses and apoptosis was observed after reperfusion. Multivariate logistic regression analysis revealed that higher tubular atrophy scores (ct) together with a lower expression of Netrin-1 might predict DGF development (training area under the receiver operating curve=0.89, cross-validated area under the receiver operating curve=0.81).
  
  
  CONCLUSIONS
  Poor baseline tubular cell quality (defined by a higher rate of tubular atrophy) combined with the reduced potential of apoptotic survival factors represented by decreased Netrin-1 gene expression were associated with delayed kidney graft function.
authors.affiliation: 1 Department of Nephrology, Transplant Center, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. 2 Transplant Laboratory, Transplant Center, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. 3 Department of Cybernetics, Faculty of Electrical Engineering, Czech Technical University, Prague, Czech Republic. 4 Department of Transplant Surgery, Transplant Center, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. 5 Clinical and Transplant Pathology Department, Transplant Center, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. 6 Address correspondence to: Ondrej Viklicky, M.D., Ph.D., Department of Nephrology, Transplant Center, Institute for Clinical and Experimental Medicine, Videnska 1958/9, 14021 Prague, Czech Republic.
authors.forename: Mariana
authors.initials: M
authors.lastname: Wohlfahrtova
authors.forename: Irena
authors.initials: I
authors.lastname: Brabcova
authors.forename: Filip
authors.initials: F
authors.lastname: Zelezny
authors.forename: Peter
authors.initials: P
authors.lastname: Balaz
authors.forename: Libor
authors.initials: L
authors.lastname: Janousek
authors.forename: Eva
authors.initials: E
authors.lastname: Honsova
authors.forename: Alena
authors.initials: A
authors.lastname: Lodererova
authors.forename: Peter
authors.initials: P
authors.lastname: Wohlfahrt
authors.forename: Ondrej
authors.initials: O
authors.lastname: Viklicky
mesh_terms: D001284:Atrophy; D001706:Biopsy; D051799:Delayed Graft Function / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D016030:Kidney Transplantation / Q000009:adverse effects*; D007684:Kidney Tubules / Q000473:pathology*; D016015:Logistic Models; D009414:Nerve Growth Factors / Q000032:analysis / Q000235:genetics*; D000075388:Netrin-1; D025341:Principal Component Analysis; D011446:Prospective Studies; D015427:Reperfusion Injury / Q000150:complications; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000235:genetics*
chemical_list: C000617351:NTN1 protein, human; D009414:Nerve Growth Factors; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1